HOG1 has an essential role in the stress response, virulence and pathogenicity of Cryptococcus gattii

Abstract

Cryptococcus gattii ( C. gattii) is a lethal pathogen that causes the majority of cryptococcosis cases in previously healthy individuals. This pathogen poses an increasing threat to global public health, but the mechanisms underlying the pathogenesis have remained to be fully elucidated. In the present study, the role of high-osmolarity glycerol (HOG)1 in the stress reaction and virulence control of C. gattii was characterized by deleting the HOG1 gene using the clinical isolate strain CZ2012, and finally, the virulence and pathogenic traits of the deletion strain were defined. Deletion of the HOG1 gene resulted in notable growth defects under stress conditions (high salt and antifungal drugs), but different traits were observed under oxidative stress conditions (hydrogen peroxide). Similarly, the C. gattii hog1Δ strains (deletion of HOG1) also displayed decreased capsule production and melanin synthesis. Furthermore, mice infected with the hog1Δ strain had longer survival times than those infected with the wild-type strain and the reconstituted strain. The hog1Δ strain recovered from infected organs exhibited significant growth defects in terms of decreased colony count and size. The present results suggested that HOG1 has a significant role in the virulence of C. gattii and these results may help to elucidate the pathogenesis of C. gattii.